营养不良可增加幼鼠齿状回颗粒下层的细胞增殖和神经生发

为了观察营养不良对幼鼠海马齿状回 (DG)和脑室下层 (SVZ)的细胞增殖和神经发生的影响 ,采用 5 -溴 -2 -脱氧尿苷(Brd U)标记结合免疫组织化学方法对脑切片分别进行 Brd U、Tu J1(β tubulin,β微管蛋白 )及 GFAP(胶质纤维酸性蛋白 )反应或双重反应。结果表明 ,营养不良幼鼠齿状回的细胞增殖和神经生发明显高于营养良好的幼鼠而脑室下层的细胞增殖数量在两者却无明显差异。在齿状回 ,新生的细胞中大约有 5 0 %为新生的神经元 ,10～ 2 0 %为神经胶质细胞。本文结果提示 ,幼鼠海马齿状回的细胞增殖和神经生发可能因营养不良而增加 ,这些新生的细胞可能对日后某些海马依赖性行为产生一定的影响     

成年哺乳动物脑内具有神经生发功能的脑室下区

成年哺乳动物脑侧脑室外侧壁的脑室下区 (SVZ)具有持续存在神经生发现象 ,表明此区存在着神经干细胞。成年神经干细胞 (adult neural stem cells)主要是指存在于成年神经系统的多能干细胞 (m ultipotent stem cells) [1 ] ,它们具有自我更新潜能 (self- renewal potential)和多向分化潜能 (m ul-tipotentiality) ,它们的子代细胞中既有与自身完全相同的细胞还有可通过非对称性分裂分化为神经元或胶质细胞的细胞。发现和分离培养以及鉴定出成年神经干细胞是近年来神经科学领域中的重大成果之一 ,它为探讨神经组织发育机制和神经组织损伤修…     

影响成年齿状回神经干细胞增殖和分化的因素

齿状回颗粒下区终生存在着神经干细胞,它们不断增殖、分化成神经元和神经胶质细胞,最终迁移到颗粒细胞层。神经干细胞在以上的动态归转过程中受到许多因素诸如激素、生长因子、神经递质、环境、行为、病变、毒物以及药物等的影响或调节。因此,揭示上述因素与神经干细胞增殖和分化的关系,对于阐明毒物的神经毒理、中枢神经系统退行性疾病和精神病的发病机制及其防治具有重要意义。     

切除嗅球对成年大鼠脑室下区神经生发功能的影响

为了探讨嗅球对成年哺乳动物侧脑室外侧壁脑室下区神经生发活动的影响 ,本研究在机械性切除成年大鼠一侧嗅球后采用连续半薄切片、克紫染色和细胞核表面三维重建技术 ,观察了侧脑室外侧壁脑室下区的细胞核表面特征及其空间位置 ,并测量了细胞核的形态学指标。结果发现 ,在切除嗅球 3个月后 ,同侧侧脑室外侧壁脑室下区的区域变小 ,特有的中、小型、形状不规则的胶质细胞核的数量比例增大 ,而具有成神经细胞核特征的细胞核 (体积较大、呈规则的椭圆体形 )数量明显减少 ,且其同型细胞核聚集现象消失。说明同侧此区的神经生发活动减弱而胶质生发 (gliogenesis)相对增强。本研究结果提示 ,哺乳动物嗅球对成年侧脑室外侧壁脑室下区的神经生发机能可能具有促进作用     

成年大鼠脑内具有神经生发功能的脑室下区的细胞形态学研究

为研究成年大鼠脑内具有神经生发功能的侧脑室外侧壁脑室下区 (SVZ)细胞的组成及特征 ,本研究对该区组织切片进行了免疫特异性反应、镀银及铅铀染色 ,在光镜和电镜下进行了观察。结果发现 ,SVZ含有能被溴脱氧尿核苷 (Brd U)标记且具有成神经细胞形态学特征的分裂后细胞 ,还有胶质纤维酸性蛋白阳性细胞和少突胶质样细胞等其他类型细胞。另外发现 ,室管膜(EL)细胞、EL深部细胞、少突胶质样细胞以及不同细胞突起所组成的网络样结构与上述 SVZ成神经样细胞紧密相邻。实验结果表明 ,SVZ成神经样细胞周围可以没有特定的胶质细胞鞘包裹 ,位于侧脑室外侧壁的不同类型细胞可能在 SVZ神经生发过程中具有不同作用。     

氯化锂促进不同年龄成年小鼠齿状回细胞增殖与神经发生

目的观察氯化锂(LiCI)对不同年龄成年小鼠齿状回细胞增殖与神经发生的影响。方法以氯化锂喂养动物,用5-溴-2’-脱氧尿核苷(BrdU)标记新生细胞,免疫组织化学染色后统计新生细胞数量;应用BrdU与TuJl／GFAP双标记,鉴别出BrdU阳性细胞的细胞类型。结果不同年龄成年小鼠齿状回的BrdU阳性细胞形态无明显差别,48周龄组阳性细胞的数量明显低于8周龄组;LiCI组小鼠新增殖细胞明显多于对照组,其中约有70％为神经元,4％～5％左右为神经胶质细胞。结论服用LiCI可显著增强成年小鼠齿状回的细胞增殖与神经发生,部分逆转其随年龄增长而逐渐减低的趋势,对于中枢神经系统退行性疾病的预防与治疗可能有重要的意义。     

嗅球切除对成年大鼠侧脑室外侧壁神经生发活动的影响

目的研究成年大鼠嗅球切除后侧脑室外侧壁（SVZ）的形态学变化,探讨嗅球对成年大鼠SVZ神经生发活动的影响。方法建立成年SD雄性大鼠右侧嗅球切除模型,并分别存活2、4、8、12周;利用Nissl染色、多唾液酸神经细胞黏附分子（PSA—NCAM）、GFAP免疫组织化学染色的方法,分别观察成年SD大鼠嗅球切除后存活不同时间两侧SVZ的组织结构和免疫组织化学特征;计数模型动物脑两侧SVZ细胞总数及PSA-NCAM、GFAP免疫阳性细胞数,并进行统计学分析。结果嗅球切除4周后,嗅球切除侧SVZ的细胞总数增加,PSA—NCAM免疫阳性细胞数增加,但GFAP免疫阳性细胞数没有明显变化;SVZ的细胞总数及PSA-NCAM免疫阳性细胞数的增加有从SVZ嘴侧向尾侧蔓延的趋势。结论嗅球切除后在SVZ仍有新生神经元不断产生,说明SVZ的神经生发活动可能并不依赖于嗅球的存在。     

孕鼠铝暴露对仔鼠齿状回神经干细胞的影响

目的:探讨孕鼠铝暴露对其仔鼠海马齿状回神经干细胞的影响.方法:雌性SD大鼠在围产期经灌胃染铝(对照组以蒸馏水、染铝组以AlCl3 100mg·kg-1·d-1灌胃),分别取胚胎18d、1月、3月龄仔代鼠脑组织,常规石蜡包埋,冠状连续切片,对海马齿状回经巢蛋白免疫组织化学显色,对阳性反应细胞进行计数,测量阳性反应产物的平均光密度.结果:染铝组子代巢蛋白免疫组织化学显色阳性细胞数均明显少于对照组,阳性反应产物平均光密度值低于对照组.结论:大鼠孕期染铝可抑制子代鼠齿状回颗粒层神经干细胞增殖,铝可能抑制海马神经发生.     

神经干细胞分化影响因素的研究进展

神经干细胞（neural stem ceils，NSCs）在体外诱导条件下，可以分化成神经系统的三种主要细胞：神经元、星形胶质细胞、少突胶质细胞。移植入动物体内它也能分化成神经元和胶质细胞并能迁移到宿主中枢神经系统（CNS）的不同部位，与宿主细胞形成突触联系。其影响因素有外部因素和内在机制两个方面，文章对生长因子、细胞因子、局部微环境等外部因素和bHLH基因转录因子、Notch信号途径、DNA甲基化等内在机制对NSCs分化影响研究进展作一综述。     

大鼠海马结构的组成、细胞类型及神经纤维联系 Ⅰ.齿状回

海马结构（hippocampalformation）不仅在学习、记忆及消绪方面发挥着重要的生理作用，而且与多种神经性和精神性疾病的发生有着密切的关系。海马结构属于古皮质，具有相对简单而高度有序化的层状结构，各种神经成分相对独立分布，使其成为研究脑皮质结构及神经纤维联系的...     

Dynamics of neurogenesis in the dentate gyrus of adult rats

Hippocampal neurogenesis declines steadily over the first year of life in the rodent, but the process persists into senescence despite a dramatic drop in the number of neurons it produces. At this point though, the survival and development patterns exhibited by new granule cells in the aging brain remain unclear in relation to patterns observed in the younger brain. The present study was carried out in order to obtain a direct quantitative comparison of hippocampal neurogenesis in juvenile and middle-aged rats with a high degree of temporal resolution, and to compare the survival and differentiation of the new cells over time. Thirty-eight-day-old and 12-month-old, male Sprague--Dawley rats were injected with 5-bromo-2'-deoxyuridine (BrdU) in order to label cells dividing in the dentate gyrus over a 24-h period, and immunohistochemical labeling was performed in order to record cell production and survival at eight different time points over the following two-month period. Using a marker of neuronally committed precursors and immature neurons (doublecortin; DCX), as well as a marker of mature neurons (calbindin d-28K; CaBP), the extent and timeline of neuronal differentiation, maturation, and migration of the new cells were also characterized. Results indicated that 12-month-old rats experienced a nearly 94% reduction in neurogenesis relative to juveniles, due almost entirely to a 92% drop in cell production. A largely preserved course of development and migration in the remaining newborn cells suggests treatments that enhance cell proliferation could be crucial in reversing the age-related decline in neurogenesis.     

Postischemic exercise decreases neurogenesis in the adult rat dentate gyrus

Running exercise enhances neurogenesis in the normal adult and aged hippocampus. However, the effect of exercise on neurogenesis in the ischemic hippocampus is unclear. Here, we show that running exercise has different effects on ischemic and non-ischemic brain. Young (3-4-month-old) normotensive Wistar rats were used for this study. We administered bromodeoxyuridine (BrdU) to rats 7 days after the induction of transient forebrain ischemia or sham operation. BrdU-labeled cells were increased in the ischemic subgranular zone (SGZ) and granule cell layer (GCL) and double immunofluoresence showed approximately 80% of BrdU-labeled cells expressed neuronal markers. To assess the effect of running exercise on neurogenesis, BrdU-labeled cells in these regions were quantified after 1 day and 14 days. In sham-operated rats, the numbers of BrdU-labeled cells were significantly increased (2.2-fold) in the SGZ and GCL in response to running exercise. The numbers of BrdU-labeled cells were increased in response to ischemia, however, they were decreased 14 days after BrdU administration and running exercise accelerated the reduction in BrdU-labeled cells in ischemic rats. These findings suggest that running exercise has a negative effect on neurogenesis in the ischemic hippocampus. This may be important with respect to assessment of therapeutic approaches for functional recovery after stroke.     

Effects of adult neurogenesis on synaptic plasticity in the rat dentate gyrus

Ongoing neurogenesis in the adult hippocampal dentate gyrus (DG) generates a substantial population of young neurons. This phenomenon is present in all species examined thus far, including humans. Although the regulation of adult neurogenesis by various physiologically relevant factors such as learning and stress has been documented, the functional contributions of the newly born neurons to hippocampal functions are not known. We investigated possible contributions of the newly born granule neurons to synaptic plasticity in the hippocampal DG. In the standard hippocampal slice preparation perfused with artificial cerebrospinal fluid (ACSF), a small (10%) long-term potentiation (LTP) of the evoked field potentials is seen after tetanic stimulation of the afferent medial perforant pathway (MPP). The induction of this ACSF-LTP is resistant to a N-methyl-D-aspartate (NMDA) receptor blocker, D,L-2-amino-5-phosphonovaleric acid (APV), but is completely prevented by ifenprodil, a blocker of NR2B subtype of NMDA receptors. In contrast, slices perfused with picrotoxin (PICRO), a GABA-receptor blocker, revealed a larger (40--50%), APV-sensitive but ifenprodil-insensitive LTP. The ACSF-LTP required lower frequency of stimulation and fewer stimuli for its induction than the PICRO-LTP. All these characteristics of ACSF-LTP are in agreement with the properties of the putative individual new granule neurons examined previously with the use of the whole cell recording technique in a similar preparation. A causal relationship between neurogenesis and ACSF-LTP was confirmed in experiments using low dose of gamma radiation applied to the brain 3 wk prior to the electrophysiological experiments. In these experiments, the new cell proliferation was drastically reduced and ACSF-LTP was selectively blocked. We conclude that the young, adult-generated granule neurons play a significant role in synaptic plasticity in the DG. Since DG is the major source of the afferent inputs into the hippocampus, the production and the plasticity of new neurons may have an important role in the hippocampal functions such as learning and memory.     

Serotonin and neurogenesis in the hippocampal dentate gyrus of adult mammals

It is well documented that in mammals new neurons are generated in the dentate gyrus (DG) and integrated into hippocampal circuits throughout their life. However, functions of these newly generated cells are still hotly debated. One of the important factors that may influence the rate of DG neurogenesis is serotonin. Apart from being a neurotransmitter and neuromodulator it plays many other roles in the central nervous system, including the role of a trophic factor influencing functional state of neurons. In this review I discuss the changing views on adult hippocampal neurogenesis then briefly describe the anatomy and function of the hippocampus, focusing on its serotonergic innervation and receptors. Further, the possible role of serotonin and the newly generated DG neurons in hippocampus-dependent memory is discussed. Finally mechanisms by which serotonin and its receptors influence neurogenesis in the adult DG are summarized and hypotheses linking the decreased rate of DG neurogenesis with mechanisms of depression are discussed.     

N-methyl-d-aspartate receptor expression during adult neurogenesis in the rat dentate gyrus

N-methyl-d-aspartate (NMDA) receptors play a crucial role in the regulation of neuronal development during embryogenesis and they also regulate the rate of neurogenesis and proliferation in the adult dentate gyrus. However, the mechanism by which they influence these processes is not fully understood. NMDA receptors seem to be functional in hippocampal precursor cells and recently generated granule neurons, although there is no anatomical correlate of these physiological observations. We have analyzed the expression of the NMDA receptor subunits NR1 and NR2B in precursor cells and recently generated granule neurons of the adult rat dentate gyrus, using 5'bromodeoxyuridine, green fluorescent protein-retrovirus and immunohistochemistry. Our results indicate that NR1 and NR2B are expressed in some proliferating cells of the adult subgranular zone. These receptors are absent from transiently amplifying progenitors (type 2-3 cells) but they are found in glial fibrillar acidic protein expressing cells in the subgranular zone, suggesting its presence in bipotential (type-1) precursor cells. NR1 and NR2B are rarely found in granule cells younger than 60 h. By contrast, many granule cells generated 14 days before killing express both NMDA receptor subunits. These results demonstrate that adult hippocampal neurogenesis may be regulated by NMDA receptors present in precursor cells and in differentiating granule neurons, although these receptors are probably not located on synapses. However, an indirect effect through NMDA receptors located in other cell types should not be excluded.     

Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus

Exposure to an enriched environment increases neurogenesis in the dentate gyrus of adult rodents. Environmental enrichment, however, typically consists of many components, such as expanded learning opportunities, increased social interaction, more physical activity and larger housing. We attempted to separate components by assigning adult mice to various conditions: water-maze learning (learner), swim-time-yoked control (swimmer), voluntary wheel running (runner), and enriched (enriched) and standard housing (control) groups. Neither maze training nor yoked swimming had any effect on bromodeoxyuridine (BrdU)-positive cell number. However, running doubled the number of surviving newborn cells, in amounts similar to enrichment conditions. Our findings demonstrate that voluntary exercise is sufficient for enhanced neurogenesis in the adult mouse dentate gyrus.     

Sustained increase in adult neurogenesis in the rat hippocampal dentate gyrus after transient brain ischemia

It is known that the number of newly generated neurons is increased in the young and adult rodent subventricular zone (SVZ) and dentate gyrus (DG) after transient brain ischemia. However, it remains unclear whether increase in neurogenesis in the adult DG induced by ischemic stroke is transient or sustained. We here reported that from 2 weeks to 6 months after transient middle cerebral artery occlusion (MCAO), there were more doublecortin positive (DCX+) cells in the ipsilateral compared to the sham-control and contralateral DG of the adult rat. After the S-phase marker 5-bromo-2'-deoxyuridine (BrdU) was injected 2 days after MCAO to label newly generated cells, a large number of BrdU-labeled neuroblasts differentiated into mature granular neurons. These BrdU-labeled neurons survived for at least 6 months. When BrdU was injected 6 weeks after injury, there were still more newly generated neuroblasts differentiated into mature neurons in the ipsilateral DG. Altogether, our data indicate that transient brain ischemia initiates a prolonged increase in neurogenesis and promotes the normal development of the newly generated neurons in the adult DG.     

Chronic high corticosterone reduces neurogenesis in the dentate gyrus of adult male and female rats

Adult neurogenesis in the dentate gyrus of the hippocampus is altered with stress exposure and has been implicated in depression. High levels of corticosterone (CORT) suppress neurogenesis in the dentate gyrus of male rats. However both acute and chronic stress do not consistently reduce adult hippocampal neurogenesis in female rats. Therefore, this study was conducted to investigate the effect of different doses of corticosterone on hippocampal neurogenesis in male and female rats. Rats received 21 days of s.c. injections of either oil, 10 or 40 mg/kg CORT. Subjects were perfused 24 h after the last CORT injection and brains were analyzed for cell proliferation (Ki67-labeling) or immature neurons (doublecortin-labeling). Results show that in both males and females high CORT, but not low CORT, reduced both cell proliferation and the density of immature neurons in the dentate gyrus. Furthermore, high CORT males had reduced density in immature neurons in both the ventral and dorsal regions while high CORT females only showed the reduced density of immature neurons in the ventral hippocampus. The high dose of CORT disrupted the estrous cycle of females. Further, the low dose of CORT significantly reduced weight gain and increased basal CORT levels in males but not females, suggesting a greater vulnerability in males with the lower dose of CORT. Thus we find subtle sex differences in the response to chronic CORT on both body weight and on neurogenesis in the dorsal dentate gyrus that may play a role in understanding different vulnerabilities to stress-related neuropsychiatric disorders between the sexes.     

Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats

During adulthood, neuronal precursor cells persist in two discrete regions, the subventricular zone[19]and the hippocampal subgranular zone,[11]as recently demonstrated in primates.[10]To date, a few factors such as adrenal steroids[9]and trophic factors[13]are known to regulate adult neurogenesis. Since neuronal activity may also influence cellular development and plasticity in brain, we investigated the effects of serotonin depletion on cell proliferation occurring in these regions. Indeed, in addition to its role as a neurotransmitter, 5-hydroxytryptamine (serotonin) is considered as a developmental regulatory signal.14, 22Prenatal depletion in 5-hydroxytryptamine delays the onset of neurogenesis in 5-hydroxytryptamine target regions[14]and 5-hydroxytryptamine promotes the differentiation of cortical and hippocampal neurons.15, 23Although in the adult brain, a few studies have suggested that 5-hydroxytryptamine may play a role in neuronal plasticity by maintaining the synaptic connections in the cortex and hippocampus,3, 6, 16no information is actually available concerning the influence of 5-hydroxytryptamine on adult neurogenesis. If further work confirms that new neurons can be produced in the adult human brain as is the case for a variety of species, it is particularly relevant to determine the influence of 5-hydroxytryptamine on neurogenesis in the hippocampal formation, a part of the brain largely implicated in learning and memory processes. Indeed, lack of 5-hydroxytryptamine in the hippocampus has been associated with cognitive disorders, such as depression,[1]schizophrenia and Alzheimer's disease.[7]In the present study, we demonstrated that both inhibition of 5-hydroxytryptamine synthesis and selective lesions of 5-hydroxytryptamine neurons are associated with decreases in the number of newly generated cells in the dentate gyrus, as well as in the subventricular zone.     

神经调控技术对海马齿状回神经发生的影响

大多数神经发生出现在最初的发育过程中,但大脑的某些区域在一生中都保持着神经发生.在成年海马齿状回中,每天都不断有新生的神经元产生,并逐渐发育、整合到原有的齿状回神经网络中去.目前观念认为海马相关的认知功能与海马齿状回神经发生有关.神经调控技术作为一种不破坏神经组织的可逆性神经外科疗法,在癫痫、疼痛、帕金森病、抑郁症、强...